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Domain Motions in Phosphoglycerate Kinase using Hierarchical NEIMO Molecular Dynamics Simulations

Vaidehi, Nagarajan and Goddard, William A., III (2000) Domain Motions in Phosphoglycerate Kinase using Hierarchical NEIMO Molecular Dynamics Simulations. Journal of Physical Chemistry A, 104 (11). pp. 2375-2383. ISSN 1089-5639. doi:10.1021/jp991985d.

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We examined the large-scale domain motions in the glycolytic enzyme phosphoglycerate kinase (PGK) using the hierarchical Newton−Euler inverse mass operator (H−NEIMO) molecular dynamics (MD) method. NEIMO is an efficient MD method for torsion-only internal coordinate dynamics method. H−NEIMO is an extension of the NEIMO method for doing coarse grain MD in which large domains of a protein are treated as rigid clusters connected by flexible torsion angles. This allows an efficient examination of the low-frequency long time scale motions. We find that with both substrates bound (Phospho glycerate and ATP) on PGK the closed domain structure is more stable than the open domain structure. During the H−NEIMO MD the two domains of the open structure come close together while the N-terminus of helix 14 (namely, Gly-394 in the R65Q yeast structure) moves close to the ATP derivative, suggesting that it could be involved in the mechanism of phosphoryl transfer. We find that residues 175−183 in the R65Q yeast ternary complex structure are important in triggering the closure of the domains, resulting in a piston-like motion of helix 7. The domain rotation axis in the all atom Cartesian MD simulations is close to that of H-NEIMO MD. The axis of domain rotation in H−NEIMO is also in the same region as the rotation axis between two experimental crystal structures. Thus, H−NEIMO captures the long time scale motions in rather short simulation times. This demonstrates that H−NEIMO is a promising mesoscale coarse grain molecular dynamics technique to determine the low-frequency long time motions responsible for the function of proteins such as PGK.

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Goddard, William A., III0000-0003-0097-5716
Additional Information:© 2000 American Chemical Society. Received 16 June 1999. Published online 12 February 2000. Published in print 1 March 2000. The authors thank Dr. Timothy McPhillips of the Stanford Synchrotron Research Laboratory for his significant help in carrying out this research, with many useful discussions. This research was funded by NSF-SGER-DBI-9708929 (Dr. Karl Koehler). The computational resources in the MSC used in this work were supported by grants from NSF-GCAG, NSF-CHEM, ARO-DARPA, ARO-MURI (Kiserow), by Beckman Institute, BP Amoco, Chevron Corp, Exxon, Seiko-Epson, Owens-Corning, Avery-Dennison, Dow Chemical, and 3M.
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Army Research Office (ARO)UNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Chevron CorporationUNSPECIFIED
Issue or Number:11
Record Number:CaltechAUTHORS:20170719-080126858
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Official Citation:Domain Motions in Phosphoglycerate Kinase using Hierarchical NEIMO Molecular Dynamics Simulations Nagarajan Vaidehi and William A. Goddard, III The Journal of Physical Chemistry A 2000 104 (11), 2375-2383 DOI: 10.1021/jp991985d
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:79185
Deposited By: Ruth Sustaita
Deposited On:19 Jul 2017 15:10
Last Modified:15 Nov 2021 17:46

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